Objetivo
This research addresses questions raised by attempts to design proteins de novo. Such polypeptides are often compact and they have a pronounced secondary structure as a rule, but a definite organisation of side chains is usually, but not always, absent. The thermodynamics of forming a protein-like structure involves competition between the favourable hydrophobic and the van der Waals effects of forming a tightly packed core versus the unfavourable entropic effect of restriction conformation. Rules for these effects to guide the systematic design of proteins are required. It will then be necessary to show that these rules can be applied to guide the synthesis of a folded protein-like molecule.
The objectives of the research are firstly, to provide the basis for the rational design of novel proteins based on the selection of residues suitable to favour thermodynamically the folded conformation, with two aspects to be considered: the close packing of residues between secondary structures compatible with a core that excludes solvent and is favoured by the hydrophobic effect; and the effect of restricting side chain mobility and its effect on the conformational entropy of protein folding.
Secondly, guided by the empirical rules the sequence of Albebetin that has previously been synthesised and expressed in milligram quantities will be examined to suggest changes that might lead to the formation of a solid core in the folded protein; and finally, other sequences of novel proteins for synthesis will be designed.
Convocatoria de propuestas
Data not availableRégimen de financiación
Data not availableCoordinador
WC2A 3PX London
Reino Unido